Related Experiment Video
Updated: Jul 10, 2026
Patient-derived Heterogeneous Xenograft Model of Pancreatic Cancer Using Zebrafish Larvae as Hosts for Comparative Drug Assessment
Published on: April 30, 2019
VK-2019 enhances gemcitabine's antitumor activity in EBV-positive nasopharyngeal carcinoma by upregulating PRODH
Chengxun Li1, Dantong Gu1, Yingzhu Li2
1Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200030, China.
Abstract:
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-driven malignancy, making the viral protein EBNA1 a pivotal therapeutic target. This study evaluates VK-2019, a clinical-stage EBNA1 inhibitor, for its potential to sensitize NPC cells to chemotherapy. We report that VK-2019 synergistically enhances gemcitabine efficacy, reducing the IC50 by nearly 30-fold in EBV-positive C666-1 cells. Transcriptomic profiling combined with in vitro and in vivo models reveals a distinct mechanism: VK-2019 inhibition of EBNA1 downregulates c-MYC, thereby derepressing its downstream target, Proline Dehydrogenase (PRODH). Furthermore, we demonstrate that gemcitabine independently upregulates PRODH via p53 pathway activation. This dual induction of PRODH drives enhanced anti-tumor cytotoxicity. These results provide a prominent preclinical rationale for evaluating VK-2019 in combination regimens and offer a potential therapeutic strategy for patients with EBV-associated nasopharyngeal carcinoma.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...